ascariasis

PIDSP Journal 2010 Vol 11 No.1 Copyright ® 2010

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35

The Antihelminthic Efficacy Of Pineapple Fruit Mebendazole On Soil Transmitted Helminthiases: A Randomized Controlled Trial

AUTHORS: Charina A. Manabo, MD, Melchor Victor G. Frias, MD

De La Salle University Medical Center

KEYWORDS

pineapple, ascariasis, trichuris, antihelminthic

ABSTRACT

Objectives: The study was performed in order compare the antihelminthic efficacy of pineapple fruit versus

mebendazole in schoolchildren.

Design: The study performed was a single, blinded randomized control trial.

Subjects: Ninety subjects aged 5 to 13 years old and positive for soil-transmitted helminthiases were

included in the study.

Methods: Eligible participants were subjected to Kato-Katz for diagnosis and quantitative ova count.

Those positive for soil-transmitted helminthes were randomized to Group A (pineapple) and Group B

(mebendazole). After 7 days of treatment, stool samples were subjected to another Kato Katz for

quantitative ova analysis. Seven hundred fifty ml of puree made from one pineapple, with approximate

weight of 750g, was given in divided amounts within 24 hours (250 ml 3x a day) for group A.

Results: Majority (77.78%) were infected with Ascaris lumbricoides. Pineapple exhibited a significant

improvement in egg reduction rate (RR) with a p-value of < 0.001 at 95% CI. This showed 83.5 % egg per

gram (epg) of feces reduction and a cure rate of 68.9%. Mebendazole also revealed a significant egg

reduction with p-value of < 0.001 at 95% CI. It also showed a remarkable egg per gram reduction rate of

92.25% and cure rate of 88.9%. There were no adverse events reported.

Conclusion: Mebendazole, as an antihelminthic, is a better choice; but pineapple fruit may be beneficial as

it had a high egg reduction rate and an acceptable cure rate.



36

INTRODUCTION

Intestinal parasitism is an important

problem in third world countries, including the

Philippines. Many studies have been made

regarding the incidence of intestinal parasitism.

As early as 1963, out of the 169 children

examined for parasitism in Caloocan City, 98%

of the isolates were ascaris lumbricoides, 65%

Trichuris trichuria, 4% hookworm, and 1%

Giardia lambia.7 Other studies showed that out

of 781 children, 85.1% were ascaris, 27.9%

were trichuris, and 34.4% hookworm. It was

also noted that among double parasitism, the

most common was the combination of ascaris

and trichuris.8

A study was conducted in 40 subjects on

the comparison of pineapple and pyrantel

pamoate on the treatment of ascariasis. Cure

rate was 55% for the pineapple group and 70%

for the pyrantel pamoate group. 24

OBJECTIVES

The objective of this study is to compare the

anti-helminthic efficacy of Pineapple Fruit to

Mebendazole among children aged 5 to 13

years old in a community setting. Safety of both

regimens will also be investigated.

MATERIALS AND METHODS

Study Design

The study is a single, blinded, Randomized

Controlled Trial.

Study Population

Children ages 5 to 13 years old, regardless of

sex, who would meet the following criteria:

positive of soil-transmitted helminthiases, e.g.

Ascaris lumbricoides, Trichuris trichuria, and

other helminths on the preliminary Kato-Katz;

had a normal physical examination prior to the

conduct of the study, and those whose parents

gave consent for their children to be included in

the study.

Patients were excluded if: they had anti-

helminthic therapy 2 weeks prior to and during

the study period; had a concomitant infection

at the time of the study, e.g. cough, colds,

fever, diarrhea; had passage of worms 2 weeks

prior to conduct of the study; or had a known

allergy to pineapple and/or mebendazole.

Sample Size Calculation

Sample size was computed based on the

cure rate of mebendazole at 90%10

and

pineapple at 59.36%. Using the Epi Info version

6, with confidence level of 95% and a power of

80%, 74 participants comprised the sample

population. An additional 20% was allocated

for drop-outs, thus 90 participants comprised

the final sample population at 45 per group.

Treatment Assignment and Randomization

Using a computer generated-randomization

list, eligible participants were assigned to either

the experimental group or the treatment

group. The experimental group was designated

as group A and was given pineapple. The

treatment group was designated as Group B

and given mebendazole.

Study Procedures and Activities

All children, whose parents consented,

were personally interviewed and examined by

the investigator. Age in years, weight in

kilograms, and height in centimeters were

determined. History of illnesses and other

symptoms, intake of antihelminthic drugs,

previous history of passage of worms, and

allergies to food and medications were asked.

Complete physical examinations were also

performed. All these data were documented

on standardized data collection forms. Eligible

participants were subjected to Kato-Katz for

diagnosis and quantitative ova count. In

addition, participants were classified as to light,

moderate, or heavy parasitic infestation

according to WHO classification. These

procedures were done until the required

sample size was reached.

All children positive for Ascaris

lumbricoides, Trichuris trichuria, and other soil-

transmitted helminths on Kato-Katz were

randomized either to Group A or Group B.

After 7 days of treatment, stool samples were

again collected from the participants and were

coded and subjected to another Kato Katz for

quantitative ova analysis. The same medical

technologist who did the preliminary Kato Katz



37

handled the second stool analysis; he was

blinded as to which group the stool sample

came from.

Fecal Sample Handling and Analysis

Each participant was given sterilized,

standard stool specimen containers. Stool

samples collected from the participants were

subjected to Kato-Katz within one hour of

collection.

Study Intervention and Administration

One peeled pineapple, weighing

approximately 750 grams, prepared as blended

fruit puree was given to each participant in

Group A. 750 ml of the puree, sweetened with

two tablespoons of sugar, was given to each to

be consumed in an entire day. On the other

hand, 500 mg mebendazole chewable tablets

were given in single doses to each participant in

group B. The administration of both

interventions was supervised by the

investigator to ensure compliance and proper

administration.

Study Outcome Measures

Kato-Katz, via microscopy by a trained

medical technologist, was used to quantify the

number of eggs per sample. The intensity of

the helminth infection is defined as eggs per

gram (epg) of feces according to the WHO

classification. Cure is defined as zero or no ova

seen on repeat Kato-Katz after intake of

pineapple or administration of mebendazole. In

addition, cure rate is defined as the difference

in the prevalence rates for each helminth

between pre- and post-treatment and is

expressed as percentage of the pre-treatment

value. The egg reduction rate is expressed as

the percentage fall in arithmetic mean egg

counts.31

These were used to determine

whether pineapple fruit is comparable with

mebendazole.

All those who had treatment failure in the

pineapple group were given the recommended

drug, 500 mg of mebendazole chewable tablet

as single dose.

Side effects for both the pineapple fruit and

mebendazole were also noted. All symptoms

noted by the mother to the child after

treatment will be enumerated.

Data Analysis

Data were encoded and an analysis was

done on them using SPSS. A paired t-test was

used to compare the quantitative ova counts

before and after treatment. Logistic regression

analysis was used to determine the relationship

between the baseline age, weight, height, pre-

treatment ova count and the reduction and

cure rate of both pineapple and mebendazole.

Outcomes were computed as follows:

Cure Rate = Number of Subjects Cured X 100

Number of Subjects Treated

Egg per Gram (epg) Reduction Rate = Mean epg before treatment – Mean epg after treatment x 100

Mean epg before treatment

Mean epg = Σ epg

N

Σepg is the sum of each individual epg and is

divided by n, the number of subjects treated.

Adverse effects Monitoring

Adverse reactions to both the drug and

pineapple were monitored by direct

observation by the author during and after

administering mebendazole and pineapple.

Parents were also advised to report and contact

the investigator if any untoward symptoms

were noted after the procedures until the time

that the second specimen was collected.

Ethical Considerations

This study was performed in accordance

with the Principles stated in the Declaration of

Helsinki. The Informed Consent form and

Information sheet were reviewed and approved

by the Bioethics Committee of the De La Salle

University Medical Center.

The investigator coordinated with the

members of the community to present the

study and get an approval. A meeting with the

barangay health workers, barangay officials and

parents was done to explain the study and all



38

its procedures. The adverse effects which may

be encountered, the persons and hospital

where they could seek medical attention was

explained to the parents and the members of

the community. A permit was secured from the

municipal mayor and municipal health officer

prior to the conduct of the study.

On the screening visit (Day 0), informed

consent was obtained from the parents or

guardian.

RESULTS

Demographic and Clinical Characteristics

Table 1 shows that there were significant

differences in some clinical characteristics of

the subjects in the two treatment groups.

Mean weight and height were significantly

lower and mean pre-treatment ova count was

significantly higher in the control group

compared to the pineapple group.

Most of the subjects in the pineapple group

had no wasting or had mild wasting (31.10 %).

On the other hand, the mebendazole group is

mostly composed of subjects with no wasting

(35.60%). Most of the subjects have mild

stunting on both the pineapple and

mebendazole group with 53.30 % and 57.80 %,

respectively (Table 2).

Among the 102 stool samples examined, 90

were positive for helminths. Ascaris

lumbricoides was the most common helminth

infection upon enrollment in the study. All

infections were of light intensity according to

the WHO classification. Majority had single

infection and 2.22% had mixed infections.

Ascaris lumbricoides and Trichuris trichuria is

the only dual infection noted among those who

had mixed infection at 2.22%.

Moreover, among those treated with

pineapple, Ascaris lumbricoides was the most

common cause of single infection (73.33%). A

similar observation was noted in the

mebendazole group. No hookworm was noted

as a cause of single infection.

Study Outcome Measures

Ova Count

Before the administration of medications

both groups had a significant difference in

terms of ova count. However, after treatment

the ova counts were significantly reduced

(Table 4).

Table 1. Baseline Characteristics of the

Subjects. Pineapple

(n = 45)

Mebendazole

(n = 45)

p

value

Sex n (%)

Male

Female

22 (48.9%)

23 (51.1%)

15 (33.3%)

30 (66.7%)

0.135

Age

Mean + SD1

8.7333+

2.10411

7.0444 +

2.64537

0.098

Weight

Mean + SD

21.1111 +

4.71931

18.5667 +

6.64773

0.019

Height

Mean + SD

120.1333 +

11.37301

107.0667 +

21.91450

0.013

Pre

Treatment

Ova Count

Mean + SD

4.4222 +

1.49983

6.3778 +

3.32545

0.001

1 Standard Deviation

Table 2. Clinical Characteristics of the Subjects. Clinical Pineapple

(n = 45)

Mebendazole

(n = 45)

Wasting according to

Waterlowes

Classification

Normal

Mild

Moderate

Severe

Total

14 (31.10%)

14 (31.10%)

11 (24.40%)

6 (13.30%)

45 (100%)

16 (35.60%)

15 (33.30%)

10 (22.20%)

4 (8.900%)

45 (100%)

Stunting according

to Waterlowes

Classification:

Normal

Mild

Moderate

Severe

Total

10 (22.00%)

24 (53.30%)

9 (20.00%)

2 (4.400%)

45 (100%)

10 (22.20%)

26 (57.80%)

3 (6.700%)

6 (13.30%)

45 (100%)



39

Table 3. Parasites Found According to the WHO Classification on Intensity of Helminthiasis On Baseline

Kato-Katz.

Intensity of

Infection

Parasite Pineapple

N = 45 (%)

Mebendazol

e

N= 45 (%)

Total

N (%)

Light

Ascaris (As) 33

(73.33%)

37

(82.22%)

70

(77.78%)

Trichuris

(Tr)

11

(24.44%)

7

(15.56%)

18

(20.0%)

As and Tr 1

(2.22%)

1

(2.22%)

2

(2.22%)

Moderate

Ascaris 0 0 0

Trichuris

trichuria

0

0

0

As and Tr 0 0 0

As, Tr and

Hookworm

0

0

0

Heavy

Ascaris 0 0 0

Trichuris 0 0 0

As and Tr 0 0 0

As, Tr and Hookworm 0 0 0

TOTAL (100%) (100%) (100%)

Table 4. Comparison of the Ova Count before and After Administration of Medication.

Pineapple Mebendazole P Value 95% CI

Before Treatment

Mean + SD

4.4222 + 1.49983

6.3778 + 3.32545

0.001

-3.03627 –

-0.87484

After Treatment

Mean + SD

0.6444 + 1.04785 0.2889 + 0.92004 0.091 -0.05754-

0.76865

Table 5. Comparison of the Ova Count In Terms of the Treatment Group before and After

Administration of Medication.

Treatment

Group

Before Treatment After Treatment P value 95% CI

Pineapple

Mean + SD

4.4222 + 1.49983 0.6444 + 1.04785 < 0.001 3.20170 – 4.35386

Mebendazole

Mean + SD

6.3778 + 3.32545 0.2889 + 0.92004 < 0.001 5.01551 – 7.16227



40

There was significant ova reduction in each

of the treatment groups. Both pineapple and

mebendazole had p values of less than 0.001

and with a 95% confidence interval. (Table 5).

Reduction and Cure Rates

There was a cure rate of 68.9 % for

pineapple fruit as compared to 88.9% for

mebendazole. In terms of the egg per gram of

feces, there was a reduction rate of 83.52 % for

pineapple and 92.3 % for mebendazole (Table

6). No adverse effects were noted for any of

the treatment groups.

Table 6. The Efficacy Measures of Pineapple

Fruit and Mebendazole.

Treatment Cure

Rate

epg¹ reduction

rate

Pineapple 68.9% 83.52%

Mebendazole 88.9% 92.3% 1

eggs per gram of feces

Table 7 shows that the significant difference

in the baseline data (age, weight, height, and

pre treatment ova count) did not affect the

reduction and cure rates of both pineapple and

mebendazole.

Table 7. Logistic Regression Analysis of the

Factors associated with the reduction and cure

rates of pineapple fruit and mebendazole.

VARIABLES SLOPE B SIG P VALUE

Ova Count

Group2

Age

Weight

Height

Constant

.137

- 1.466

0.048

.322

-.071

3.125

.371

.059

.858

.100

.286

0.027

Adverse Effects Monitoring

None of the parents or subjects complained of

any problems related to the administration of

both the medicine and the fruit.

DISCUSSION

Demographic and Clinical Characteristics

Based on the Waterlowes' classification on

wasting and stunting, most of the participants

included in this study had normal to mild

wasting and with mild stunting. In a study done

in 2001 by Andrade, et. al., mean age was

noted at 8.9 years old; children included in his

study were below the third percentile and were

noted to be stunted and wasted.32

Majority of the children included in the

study were infected with Ascaris lumbricoides

only, followed by Trichuris trichuria. If

combined, Ascaris and Trichuris was the most

common co infection. Same results were noted

by Akbar, et. al. with regard to frequency of

ascaris and trichuris infestation.33

A study done

in Zamboanga (2004) revealed that the most

prevalent parasite was Ascaris lumbricoides.34

All parasitic infections noted in this study

were of light intensity according to the WHO

classification. A study by Albonico likewise

noted that most of the children included in his

study had light helminth infestation.35

The baseline, clinical characteristics of

weight, height, and pretreatment ova count

were significantly different in the two groups.

This implies that randomization was not able to

distribute these known variables, more or less,

equally to the two groups; thus there is a

possibility that the outcomes could be affected

by bias. However, statistical analysis revealed

that these factors did not affect the reduction

and cure rate in both groups.

Recently, a study was conducted on the

comparison of pineapple and pyrantel pamoate

on the treatment of ascariasis. Said study used

3 slices of pineapple, 2 centimeters thick, to be

eaten after meals and for 7 days; this was

compared to a single dose of pyrantel pamoate

at 11 mg/kg/dose. The efficacy was measured

by comparing the cure rates: it is a complete

cure if the stool exam turned out negative or if

there is a reduction rate of >50% after one

week of treatment. The results of the stool

exam showed that one week of treatment

noted a 55% complete cure for pineapple fruit



41

and a 70% cure rate for pyrantel pamoate.

However, the study was limited to 40

subjects.24

For this study, both treatment groups had

significant improvements in the reduction of

ova count after 7 days of treatment.

Moreover, in each of the treatment groups,

pineapple fruit had a notable egg reduction

rate of 83.52%, 7 days after its administration.

These findings are also noted in the study of

Adriano, which claimed an egg reduction rate

of greater than 50% in 17 out of 20 subjects.25

In other studies, pineapple leaves were also

used—noting a dramatic reduced egg counts of

greater than 90% after 10 days of

administration.6 However, it is to be noted that

the reduction rate in this study is based only on

light infection according to WHO classification.

On the other hand, mebendazole has an

egg reduction rate of 92.25% after 7 days of its

administration. A high egg reduction rate of

99.1 % with mebendazole was likewise noted

by Albonico in 1994.35

In another study conducted by Legese, et.

al.36

, mebendazole was shown to have a cure

rate of 96%. According to the WHO,

mebendazole has a cure rate of 60% to 89 %

against Trichuris, and more than 90 % cure rate

for Ascaris.37

No adverse events or complications were

noted in both treatment groups, which implied

that both interventions were well tolerated and

safe.

Active Ingredients in Pineapple

Pineapples have proteolytic enzyme—

bromelain, that aids in digestion.22

In 1989 at

MCU Manila, isolation of the enzyme bromelain

from pineapple fruit was made. This study

noted that the percent yield of bromelain from

pineapple juice was 0.1965%. The anti-

helminthic products, which were compounded

in the form of suspension gave an acceptable

quality when used to kill the ascaris worms.23

However, this study did not mention whether

the pineapple juice used was commercially

made or was fresh. Another study was done in

UPLB on the anti-helminthic property of

pineapple. In this study, pineapple leaves were

used; it demonstrated reduced egg counts in

nematode-infected cattle. The egg count

reduction after 10 days was as good as 90%,

compared to the control group treatment,

which was a broad spectrum commercial

product.6

Bromelain’s primary component is

sulfhydryl proteolytic fraction. It also contains

peroxidase, acid phosphatase, and several

protease inhibitors. It is not heat-stable and it

exhibits its activity over a pH range of 4.5 to

9.8.26

Bromelain has a very low toxicity, with an

LD50 greater than 10g/kg body weight.

Dosages of 1.5g/kg/day administered to rats

showed no carcinogenic or teratogenic effect.27

In humans, side effects have not been

observed. Dosage of up to 460 mg revealed no

effect on heart rate or blood pressure.

However, in doses above 700mg, palpitations

and subjective discomfort have been

reported.28

It is also a potential allergen

particularly in IgE-mediated respiratory

allergies.29

It has been shown to have

therapeutic benefits in doses of as low as

160mg/day and had best results when given in

doses above 500mg/day.

CONCLUSIONS

This study shows that the mean age of

parasitism in children was 8 years old; with

normal to mild wasting and with mild stunting:

all infections were of light intensity according

to the WHO classification. Of the 90 infected

subjects, 97.78 % were singly infected with

Ascaris lumbricoides, 2.22 % had mixed

infections of Ascaris lumbricoides and Trichuris

trichuria. The cure rate of pineapple fruit is 68.9

% as compared to 88.9% for mebendazole. In

terms of the egg per gram of feces, there is a

reduction rate of 83.5 % and 92.25 % for

pineapple and mebendazole, respectively. No

adverse effects were noted after administration

of both pineapple and mebendazole.



42

Mebendazole is a better choice as an

antihelminthic drug because it is more

efficacious. However, the pineapple fruit may

also be beneficial since it has a relatively high

egg reduction rate and an acceptable cure rate.

RECOMMENDATIONS

The following recommendations are made to

improve the results in terms of cure rate and

egg reduction rate:

1. To obtain the Bromelain content of one

pineapple fruit for proper dosaging.

2. To use different preparations and

dosages of pineapple fruit to obtain

better cure rate and reduction rate.

3. To apply pineapple fruit to subjects with

moderate to heavy intensity for a better

assessment of its antihelminthic

property.

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